Transmission of malaria from one human to another depends upon the successful sporogonic development of the parasite in vector mosquitoes. If the mosquito does not allow the ingested parasites to develop they die, and the transmission of malaria is blocked. Interruption of the malaria parasite development in vector mosquitoes could, therefore, be a useful strategy to block the spread of malaria. To design such strategies, however, understanding of the molecular, biochemical and cellular aspects of parasite development in vector mosquitoes is essential. Development of the malaria parasite in the mosquito is complex. After being ingested by a susceptible mosquito, the parasite follows an elaborate developmental scheme. Expression of stage-specific parasite genes and interaction of the parasite with various tissues and molecules in the mosquitoes, accompany dramatic morphologic changes. Each of the developmental changes is compartmentalized in distinct cellular and biochemically defined region, and occur sequentially. The development in the mosquito, therefore, is a challenge to the parasite. Most parasites do not develop to mature ookinetes in the midgut lumen or fail to invade the in the midgut wall. Therefore, molecules involved with the parasite/mosquito midgut interaction are crucial determinants of the sporogonic development of the parasite. To identify the molecules we investigate the ookinete interaction with the midgut epithelium and the survival of the parasite in the vector. Also of the hundreds of mosquitoes only a few species allow Plasmodium development, and of these a few are vectors. Even in the mosquitoes that are known as good vectors of malaria only a fraction of the ingested parasite survives. These suggest that all mosquitoes are inherently refractory to malaria parasites. Understanding the mechanism of parasite killing by mosquitoes can be useful in designing malaria transmissiojn blocking strategies. We, therefore, study insect responses to malaria parasites. These studies may lead to development of novel strategies to control malaria.